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Is the epithelial rests of Malassez a signal center that controls periodontal tissue homeostasis?

Research Project

Project/Area Number 18K09526
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57010:Oral biological science-related
Research InstitutionIwate Medical University

Principal Investigator

Keishi Otsu  岩手医科大学, 歯学部, 准教授 (60509066)

Co-Investigator(Kenkyū-buntansha) 原田 英光  岩手医科大学, 歯学部, 教授 (70271210)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsマラッセ上皮遺残 / Hertwig上皮鞘 / 歯周組織 / 歯根 / 恒常性 / 歯根膜 / Hertwig上皮 / EMT / MET / RhoAシグナル / マラッセの上皮遺残 / 上皮間葉転換 / 恒常性維持
Outline of Final Research Achievements

In this study, we aimed to elucidate the role of epithelial rests of Malassez (ERM) in periodontal tissue and the molecular mechanism of its formation process. As a result, we showed that ERM was required for the formation and maintenance of periodontal tissue, and that EMT/MET switching via RhoA signal occurred in the process of ERM formation from the Hertwig epithelial root sheath (HERS). Furthermore, we suggested that RhoA signal contributed to the formation and maintenance of periodontal tissue by controlling the expression of EMT/MET-related transcription factors and the secretion of growth factors in ERM.

Academic Significance and Societal Importance of the Research Achievements

これまでERMが歯周組織で何らかの機能を果たしていることが推測されてきたが、直接的な解明には至っていなかった。これに対して本研究は、これまで傍証のみであったERMが持つ歯周組織形成,維持の役割に実験的エビデンスを提示した。さらに我々はHERSから細胞が離脱してERMが形成される様子を実際に捉えることに成功した。このことはERM形成メカニズム論争に終止符を打つ決定的な証拠を提示した画期的成果である。また,RhoAシグナルがERMの形成,歯周組織組形成,維持に重要な働きしていることなどの新たな知見が得られ,これらは今後の歯根・歯周組織研究における新たな研究領域の創生に寄与すると期待できる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (25 results)

All 2021 2020 2019 2018

All Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (18 results) (of which Int'l Joint Research: 11 results,  Invited: 3 results)

  • [Journal Article] A novel cyclic peptide (Naturido) modulates glia?neuron interactions in vitro and reverses ageing-related deficits in senescence-accelerated mice2021

    • Author(s)
      Ishiguro Shinichi、Shinada Tetsuro、Wu Zhou、Karimazawa Mayumi、Uchidate Michimasa、Nishimura Eiji、Yasuno Yoko、Ebata Makiko、Sillapakong Piyamas、Ishiguro Hiromi、Ebata Nobuyoshi、Ni Junjun、Jiang Muzhou、Goryo Masanobu、Otsu Keishi、Harada Hidemitsu、Suzuki Koichi
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 1 Pages: 0245235-0245235

    • DOI

      10.1371/journal.pone.0245235

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxygen regulates epithelial stem cell proliferation via RhoA-actomyosin-YAP/TAZ signal in mouse incisor2021

    • Author(s)
      Otsu Keishi、Ida-Yonemochi Hiroko、Ikezaki Shojiro、Ema Masatsugu、Hitomi Jiro、Ohshima Hayato、Harada Hidemitsu
    • Journal Title

      Development

      Volume: 148 Issue: 4

    • DOI

      10.1242/dev.194787

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lamellarin 14, a derivative of marine alkaloids, inhibits the T790M/C797S mutant epidermal growth factor receptor2021

    • Author(s)
      Nishiya Naoyuki、Oku Yusuke、Ishikawa Chie、Fukuda Tsutomu、Dan Shingo、Mashima Tetsuo、Ushijima Masaru、Furukawa Yoko、Sasaki Yuka、Otsu Keishi、Sakyo Tomoko、Abe Masanori、Yonezawa Honami、Ishibashi Fumito、Matsuura Masaaki、Tomida Akihiro、Seimiya Hiroyuki、Yamori Takao、Iwao Masatomo、Uehara Yoshimasa
    • Journal Title

      Cancer Science

      Volume: - Issue: 5 Pages: 1963-1974

    • DOI

      10.1111/cas.14839

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional Expression of Sodium-Dependent Glucose Transporter in Amelogenesis.2020

    • Author(s)
      Ida-Yonemochi H, Otsu K, Harada H, Ohshima H.
    • Journal Title

      Journal of Dental Research

      Volume: - Issue: 8 Pages: 1-10

    • DOI

      10.1177/0022034520916130

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mast4 knockout shows the regulation of spermatogonial stem cell self-renewal via the FGF2/ERM pathway2020

    • Author(s)
      Lee Seung-Jun、Park Jinah、Lee Dong-Joon、Otsu Keishi、Kim Pyunggang、Mizuno Seiya、Lee Min-Jung、Kim Hyun-Yi、Harada Hidemitsu、Takahashi Satoru、Kim Seong-Jin、Jung Han-Sung
    • Journal Title

      Cell Death & Differentiation

      Volume: 20 Issue: 5 Pages: 1441-1454

    • DOI

      10.1038/s41418-020-00670-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Melnick-Needles syndrome associated molecule, Filamin-A regulates dental epithelial cell migration and root formation2020

    • Author(s)
      Hino Ryoko、Yamada Aya、Chiba Yuta、Yoshizaki Keigo、Fukumoto Emiko、Iwamoto Tsutomu、Maruya Yuriko、Otsu Keishi、Harada Hidemistu、Saito Kan、Fukumoto Satoshi
    • Journal Title

      Pediatric Dental Journal

      Volume: 30 Issue: 3 Pages: 208-214

    • DOI

      10.1016/j.pdj.2020.09.003

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effective Differentiation of Induced Pluripotent Stem Cells Into Dental Cells.2019

    • Author(s)
      Kim EJ, Yoon KS, Arakaki M, Otsu K, Fukumoto S, Harada H, Green DW, Lee JM, Jung HS.
    • Journal Title

      Dev Dyn

      Volume: Jan;248(1) Issue: 1 Pages: 129-139

    • DOI

      10.1002/dvdy.24663

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Oxygen regulates dental epithelial stem cell proliferation via RhoA-actomyosin-YAP/TAZ signal.2020

    • Author(s)
      Keishi Otsu,Hiroko Ida-Yonemochi,Shojiro Ikezaki,Hayato Ohshima,Hidemitsu Harada
    • Organizer
      2020 ISSCR Virtual
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 成熟期エナメル芽細胞のプロトンポンプの新規機能2020

    • Author(s)
      大津圭史,池崎晶二郎,原田英光
    • Organizer
      第62回歯科基礎医学会学術大会 webセミナー
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] マウス付着上皮細胞培養法と細胞株樹立2020

    • Author(s)
      池崎昌二郎,熊上-坂野深香 大津圭史,原田英光
    • Organizer
      第3回岩手県歯科医師会・岩手医科大学歯学会共済シンポジウム 第90回岩手医科大学歯学会例会
    • Related Report
      2020 Annual Research Report
  • [Presentation] エナメル質形成におけるカルシウムトランスポーター局在制御メカニズム2020

    • Author(s)
      大津圭史,稲葉 陽,池崎晶二郎,森川和政,原田英光
    • Organizer
      第126回 日本解剖学会総会・全国学術集会 第98回 日本生理学会大会合同大会 公募シンポジウム Ca2+シグナルの多彩な生理機能細胞内オルガネラから末梢組織、全身まで
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] エナメル芽細胞におけるLPAシグナルの機能的役割2020

    • Author(s)
      稲葉陽, 大津圭史, 池崎晶二郎, 荒井春乃, 森川和政, 原田英光
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] エナメル芽細胞におけるLPAシグナルの機能的役割2020

    • Author(s)
      稲葉陽,池崎昌二郎,原田英光,大津圭史
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] MAST4 regulates spermatogonial stem cell self-renewal through ERM transcription factor2020

    • Author(s)
      Seung-Doo Lee, Keishi Otsu, Dong-Joon Lee, Min-Jung Lee, Pyunggang Kim, Jinah Park, Seong-Jin Kim, Han-Sung Jung
    • Organizer
      Japan-Korea joint seminar & Frontier meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Functional role of LPA signal in ameloblasts2020

    • Author(s)
      稲葉陽,池崎晶二郎,原田英光,森川和政,大津 圭史
    • Organizer
      Japan-Korea joint seminar & Frontier meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Dysfunction of Rho Signal in Ameloblasts Occurs Amelogenesis Imperfecta and Odontogenic Cysts via EMT2020

    • Author(s)
      原田英光,池崎晶二郎,稲葉陽,大津 圭史
    • Organizer
      Japan-Korea joint seminar & Frontier meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regulation of dental epithelial stem cell fate decision by hypoxia-RhoA-YAP/TAZ signal.2020

    • Author(s)
      大津 圭史,池崎晶二郎,大島勇人,原田英光
    • Organizer
      Japan-Korea joint seminar & Frontier meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The impact of microenvironment oxygen level on cell fate decision of dental epithelial stem cells2019

    • Author(s)
      Keishi Otsu,Hayato Ohshima,Hidemitsu Harada
    • Organizer
      The 7th Tripartite Conference on Tooth and Bone in Development & Regeneration
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] THE HYPOXIC MICROENVIRONMENT MAINTAIN DENTAL EPITHELIAL STEM CELLS VIA RHOA-YAP/TAZ SIGNAL.2019

    • Author(s)
      Keishi Otsu,Shojiro Ikezaki,Hayato Ohshima,Hidemitsu Harada
    • Organizer
      2019 ISSCR/KSSCR International Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] エナメル上皮幹細胞運命決定機構における低酸素―細胞内シグナル連間2019

    • Author(s)
      大津 圭史,池崎 昌二郎,大島勇人,原田 英光
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Nobel role of vacuolar type proton-pump (V-ATPase) at maturation stage of amelogenesis2019

    • Author(s)
      Hidemitsu Harada,Shojiro Ikezaki,Keishi Otsu,Naomi Matsumoto,Ge-Hong,Sun Wada,Yoh Wada,Mayumi Nakanishi-Matsui
    • Organizer
      The 7th Tripartite Conference on Tooth and Bone in Development & Regeneration
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Dental epithelial stem cells are maintained under condition of low oxygen level.2019

    • Author(s)
      Keishi Otsu,Shojiro Ikezaki,Hayato Ohshima,Hidemitsu Harada
    • Organizer
      The 2019 TMD (Tooth Morphogenesis & Differentiation) meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Craniofacial Bone Regeneration using iPS Cell-Derived Neural Crest Like Cells2019

    • Author(s)
      Kazuko Kikuchi,Tomoyuki Masuda,Naoki Fujiwara,Akiyoshi Kuji,Hiroyuki Miura,Han-Sung Jung,Hidemitsu Harada,Keishi Otsu
    • Organizer
      第28回硬組織再生生物学会 学術大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Role of vacuolar proton-pumps (V-ATPase) at maturation stage of amalogenesis2019

    • Author(s)
      Shojiro Ikezaki,Keishi Ots,Naomi Matsumoto,Mayumi Nakanishi-Matsui,Hidemitsu Harada
    • Organizer
      The 2019 TMD (Tooth Morphogenesis & Differentiation) meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Oxygen levels regulate cell fate of mouse dental epithelial stem cells via RhoA signaling2018

    • Author(s)
      Keishi Otsu, Hidemitsu Harada
    • Organizer
      International society for stem cell research (ISSCR) 2018 annual meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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